Clinical Trials (PDQ®)

Phase III Randomized Study Substituting CTX for IFF in VAIA (Alternating VCR/DOX/IFF and VCR/DACT/IFF) for Standard-Risk Ewing's Sarcoma, of Adding VP-16 to VAIA (EVAIA) for High-Risk Patients, and of Hyperfractionated vs Conventional Definitive and Postoperative Radiotherapy. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

Combination Chemotherapy Plus Surgery and Radiation Therapy in Treating Patients With Ewing's Sarcoma. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

I. Determine whether morbidity can be reduced while preserving survival by
substituting cyclophosphamide for ifosfamide in adjuvant combination
chemotherapy in standard-risk patients with Ewing's sarcoma or peripheral
neuroectodermal tumor (PNET).
II. Determine whether survival is improved without unacceptable toxicity for
high-risk patients with Ewing's sarcoma or PNET by the addition of etoposide
to the VAIA regimen (vincristine/doxorubicin/ifosfamide/dactinomycin).
III. Evaluate the impact of surgery and conventional vs. hyperfractionated
radiotherapy (definitive and adjuvant) on local control, overall survival, and
morbidity in these patients.
IV. Relate treatment outcome with patient characteristics, histologic subtype
at diagnosis, and histologic response to neoadjuvant treatment.
V. Evaluate prospectively ifosfamide-induced nephrotoxicity and
doxorubicin-induced cardiotoxicity.

Entry Criteria

Disease Characteristics:

Biopsy-proven Ewing's sarcoma, atypical Ewing's sarcoma, and
peripheral neuroectodermal tumors
No soft tissue Ewing's sarcoma or other small cell sarcomas of
soft tissue
Such patients should be treated on the appropriate national
Soft Tissue Sarcoma Protocol
Treatment must begin within 3 weeks after diagnostic biopsy
Registration must occur within 6 weeks after initiation of
treatment

Prior/Concurrent Therapy:

No prior therapy, including primary definitive local therapy

Patient Characteristics:

Age:
Not over 35

Expected Enrollment

It is anticipated that 600 patients (200 standard-risk and 400 high-risk) will
be accrued over 4 years.

Outline

Randomized study. Patients are initially stratified as STANDARD RISK (tumor
volume at diagnosis < 100 ml) and HIGH RISK (tumor volume at diagnosis at
least 100 ml or, if < 100 ml, metastasis present). All patients receive 14
courses of chemotherapy, administered q 3 weeks throughout protocol treatment.
Standard-risk patients receive 4 courses of NEOADJUVANT CHEMOTHERAPY on
Regimen A, while high-risk patients are randomized on Arms I and II for 4
courses of neoadjuvant chemotherapy. LOCAL THERAPY is usually initiated on
week 12, after 4 courses of neoadjuvant chemotherapy, and consists of either
total removal of the tumor-bearing compartment, intracompartmental surgery
(with or without adjuvant radiotherapy), or definitive radiotherapy alone; the
choice is dictated by the site, tumor size, and patient age, among other
variables. Postoperatively, all patients receive 10 courses of ADJUVANT
CHEMOTHERAPY (plus adjuvant radiotherapy when given); standard-risk patients
are randomized on Arms III and IV, while high-risk patients receive the same
regimen to which they were assigned at initial randomization. When given,
adjuvant radiotherapy begins on week 19 and is administered concurrently with
chemotherapy.
As a variant of this general plan, patients with < 50% regression of the
soft tissue component of their tumors at restaging after 2 courses of
neoadjuvant chemotherapy (slow response) may receive preoperative irradiation,
beginning on week 7, concomitantly with the third and fourth courses of
chemotherapy.
The following acronyms are used:
CTX Cyclophosphamide, NSC-26271
DACT Dactinomycin, NSC-3053
DOX Doxorubicin, NSC-123127
IFF Ifosfamide, NSC-109724
Mesna Mercaptoethane sulfonate, NSC-113891
VCR Vincristine, NSC-67574
VP-16 Etoposide, NSC-141540
NEOADJUVANT CHEMOTHERAPY.
Regimen A (Standard risk): Alternating 3-Drug Combination Chemotherapy
Regimens. VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF.
Arm I (High risk): Alternating 3-Drug Combination Chemotherapy Regimens.
VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF.
Arm II (High-risk): Alternating 4-Drug Combination Chemotherapy Regimens.
EVAIA: VP-16/VCR/DOX/IFF alternating with VP-16/VCR/DACT/IFF.
LOCAL THERAPY.
Surgery: Resection of entire tumor-bearing compartment, including bone and
soft tissue, when possible, is the treatment of choice. The range of possible
surgical procedures includes: radical resection (e.g., amputation), wide
resection (en bloc removal of the entire tumor-bearing compartment), marginal
surgery (en bloc removal, but resection line runs through pseudocapsule and
microscopic residual disease is likely), intralesional resection (tumor
incised with contamination of surgical field), and no resection.
Radiotherapy: There are 3 settings in which radiotherapy is delivered in
these patients: as definitive treatment when definitive surgery is not
feasible, as postoperative adjuvant treatment, and preoperatively in patients
with a slow response to neoadjuvant chemotherapy. Patients who are to receive
definitive and postoperative adjuvant treatment are randomized between
conventional fractionation and hyperfractionated accelerated split-course
delivery; individuals receiving preoperative irradiation are not randomized
for radiotherapy schedule but are assigned nonrandomly to receive the
hyperfractionated accelerated split-course scheme (conventional fractionation
requires that DOX and DACT be eliminated from concomitant chemotherapy,
whereas these agents can be continued during the hyperfractionated schedule).
Individual institutions may elect not to randomize for the radiotherapy
fractionation scheme, i.e., to treat all patients on one schedule or the
other; in such institutions, all patients must follow the same scheme, decided
upon prior to treatment of the first patient. Use of photons with energies of
4-6 MV (including Co60) is recommended for extremity lesions, and 6-15 MV
energies are recommended for trunk lesions; electrons may be considered for
small superficial boosts, but are not adequate as a sole modality.
ADJUVANT THERAPY.
Arm III (Standard risk): Alternating 3-Drug Combination Chemotherapy
Regimens. VACA: VCR/DOX/CTX alternating with VCR/DACT/CTX.
Arm IV (Standard risk): Alternating 3-Drug Combination Chemotherapy Regimens.
VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF.
High-risk patients continue with 10 additional courses of VAIA or EVAIA
according to original randomization.
Adjuvant Radiotherapy, when administered, begins on week 19, and is given
concomitantly with chemotherapy.

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.